CHAPTER 85

Craniofacial Anomalies

Carol D. Berkowitz, MD, FAAP

A neonate may be born with a readily apparent craniofacial anomaly, such as cleft lip, cleft palate, or microtia, or anomaly may emerge as an infant ages. The latter includes conditions that may be genetically based but do not manifest until later, such as facial asymmetry (ie, hemifacial microsomia) and premature closure of 1 or more sutures. Alternatively, these anomalies may be environmentally influenced, such as positional or deformational plagiocephaly. Deformational plagiocephaly is defined as a condition in which an infant’s head and sometimes face are misshapen as a result of prenatal and, in recent years, postnatal external molding, which occur on the infant’s malleable cranium.

Epidemiology

The overall prevalence of cleft lip with or without cleft palate is 1 in 1,000 and that of isolated cleft palate is 1 in 2,500 live births. Cleft lip with or without cleft palate is the second most common birth defect in the United States, after Down syndrome, with nearly 7,000 infants with clefts born annually. Racial, ethnic, and geographic variation exists in the prevalence of clefts. For example, the prevalence of clefts in parts of the Philippines is 1 in 200. Similarly, cleft lip with or without cleft palate is most common among Asians and Native Americans (1 in 500) and least common among blacks (1 in 22,500). The sex distribution varies with the type of cleft. Isolated clefts of the palate occur twice as frequently in girls, but clefts of the lip with or without clefts of the palate appear twice as often in boys.

The type of cleft, the sex of the child, and whether a parent or sibling(s) is similarly affected influence the risk for recurrence of clefts in subsequent offspring. Generally, the risk for recurrence of clefts is 4% to 7% for cleft lip with or without cleft palate and 3% for isolated cleft palate.

Clefts may occur as isolated findings or as part of syndromes or sequences. In Van der Woude syndrome, clefts of the lip or palate are associated with lip pits. This condition is inherited in an autosomal-dominant manner and is the most common cause of syndromic cleft lip. Currently, more than 500 Mendelian syndromes are associated with clefts, with approximately 30% of newborns with clefts having other congenital anomalies associated with specific syndromes. Pierre Robin sequence includes micrognathia and glossoptosis (ie, retrodeviated tongue) and a distinct U-shaped cleft. One theory relates the sequence to failure of the fetal neck to extend normally, resulting in compression of the mandible on the chest, thereby restricting its growth and causing malposition of the tongue, thus preventing closure of the palate.

True craniosynostosis occurs in approximately 1 in 2,000 to 3,000 live births, and this prevalence is the same in all ethnic groups. Sex variation exists among the different types of craniosynostosis. Deformational plagiocephaly is reported in 25% to 45% of infants. The term plagiocephaly comes from the Greek plagio, meaning oblique, twisted, or slanted, and kephale for head. Firstborn and male sex increase the risk of deformational plagiocephaly at birth. Most cases of deformational plagiocephaly resolve over time without specific medical intervention.

Microtia is less common and occurs in 1 in 6,000 to 8,000 live births. Other ear malformations, such as auricular dystopia (ie, ear located on the check) or total atresia of the external area, are less common and can be associated with other syndromes. Other ear anomalies involve protuberant ears (sometimes referred to as “outstanding ears”) or pinna with folds or flattened components (eg, antihelix).

Clinical Presentation

Most craniofacial anomalies are readily apparent (Box 85.1). Some anomalies, such as cleft lips or microtia, are noted immediately in the delivery room. Other anomalies, such as craniosynostosis, develop over time. Because the onset of craniosynostosis may be gradual, the parent(s)/guardian(s) may not recognize the condition, which usually appears as asymmetry of the face or skull. Deformational plagiocephaly also evolves over time and is more often noted by the physician rather than the parent or guardian.

The child with craniofacial anomaly may also have medical problems that occur secondary to the deformity. The newborn or infant with cleft palate may present with failure to thrive because of difficulty feeding. The older infant or the child may experience recurrent otitis media, speech impairment, or psychosocial stress. Nasal regurgitation of liquids may occur in the child with obvious palatal cleft or more subtle deformity, such as submucosal cleft of the soft palate.

Pathophysiology

Clefts of the lip and palate (Figure 85.1) are believed to develop as a result of an interruption in the merging of the middle and lateral portions of the face during the sixth to seventh week of gestation. The palate normally closes with an anterior to posterior progression. Any interference with this progression (eg, tumor or encephalocele in the roof of the mouth) leads to a cleft. A vascular disruption may also result in ischemia in the involved areas. Although the etiology of clefts is not fully determined, it is felt to be multifactorial. Multiple genetic risk loci have been associated with nonsyndromic cleft lip with or without cleft palate. The interferon regulatory factor 6 (IRF6) gene is consistently associated with nonsyndromic cleft lip and palate. As with other clinical conditions, genetic predisposition interacts with environmental factors to increase the risk of the emergence of a disorder. A newborn with the A2 form of the transforming growth factor-α (TGFA) gene is 8 times more likely to have a facial cleft if the mother smokes. Other environmental teratogens associated with clefts include hydantoin, alcohol, warfarin, trimethadione, thalidomide, aminopterin, and topiramate.

Figure 85.1. Cleft lips. A, Unilateral, complete cleft lip. B, Unilateral, incomplete cleft lip. C, Bilateral, complete cleft lip.

The presence of a cleft palate affects normal oropharyngeal functioning, including sucking and speech. A child may exhibit hypernasal speech caused by the escape of air through the nose and have articulation problems. Recurrent otitis media seems to be related to dysfunction of the eustachian tube.

Facial asymmetry may be the result of hemifacial microsomia either in isolation or as part of a syndrome. Facial asymmetry that is only noted with crying is referred to as “asymmetric crying facies.” The condition is present at birth and caused by congenital hypoplasia of the depressor anguli oris muscle (CHDAOM). Although the disorder may occur in isolation, it may also occur in association with other anomalies, including congenital heart disease (40%–50%), head and neck anomalies (45%–50%), skeletal defects (22%), and genitourinary anomalies. Syndromes with which CHDAOM has been associated include CATCH 22, Cayler cardiofacial, VACTERL, and DiGeorge. As with other craniofacial anomalies, the presence of CHDAOM indicates the need for a thorough physical examination for other findings.

Microtia, a small atretic pinna of the ear, results from failure of development of the pinna and portions of the external auditory canal. It is most likely caused by a vascular accident during the 12th week of gestation. Similar anomalies have been created in laboratory animals by ligature of the stapedial artery. Microtia is considered in the spectrum of branchial arch defects.

Craniosynostosis refers to the premature closure of the sutures, which should remain open until 2 to 3 years of age. The newborn skull consists of membranous bones that meet at the suture lines. The newborn skull is therefore moldable, can change during the birthing process, and can expand in response to growth of the brain. Premature closure of the sutures is a pathologic process. What initiates this pathologic ossification is unclear. Some evidence exists to suggest that skull compression, such as that which occurs in utero with breech presentation or twins, contributes to the process. The presence of other associated anomalies, such as syndactyly, is suspicious for embryologic disturbances in fibrocartilaginous development. Abnormalities in 1 region of chromosome 10 are implicated in syndromic synostosis. Genes associated with fibroblast growth factor receptor have been implicated in some genetic syndromes with craniosynostosis. Any or all of the sutures can be affected, and the closure may result in asymmetry of the skull or microcephaly. Single suture synostosis is classified as simple; multiple synostosis is classified as compound. When closure is related to pathology at the suture, the condition is primary. In the presence of underlying brain pathology, the disorder is secondary. Premature closure of all sutures is often associated with diseases of the central nervous system, with failure of the brain to grow.

Microcephaly may result from premature closure of some or all of the sutures as a primary event or from impairment of the brain and its growth related to some other problem, such as hypoxic encephalopathy or congenital infection. Other disorders involving head size include macrocephaly, in which the head circumference is greater than the 97th percentile. Macrocephaly has numerous causes, including hydrocephalus, characterized by enlargement of the ventricular system, and macrencephaly, the latter of which may be caused by enlargement of the brain from anatomic or metabolic conditions, including mucopolysaccharidoses. The child with a large head and who is neurologically normal has benign or idiopathic macrencephaly. Measuring parental head size is frequently a clue to the correct diagnosis.

Fusion of individual sutures prevents growth of the skull perpen-dicular to the suture, and skull expansion proceeds in an axis parallel to that of the suture (Figure 85.2). If the sagittal suture fuses prematurely, the head is long and narrow, a condition referred to as scaphocephaly (“boat head”). This is the most common type of craniosynostosis, occurring in approximately 54% to 58% of cases of craniosynostosis. If the coronal sutures fuse too soon, the head is flattened; this condition is called brachycephaly and occurs in 18% to 29% of cases of craniosynostosis. The prevalence is 1 in 10,000 live births. Unilateral fusion of a coronal suture produces facial asymmetry and a characteristic appearance of the orbit on the affected side, called a harlequin deformity, noted on facial radiography. Premature closure of the metopic suture results in the triangular-shaped head characteristic of trigonocephaly, reported in 4% to 10% of case of craniosynostosis. Familial cases have been reported, as well as abnormalities of chromosomes 3, 9, and 11. The FGFR3P25OR mutation has been reported in patients with nonsyndromic craniosynostosis, particularly with coronal or multisuture synostoses.

Premature closure of the lambdoid sutures results in plagiocephaly (ie, oblique head) (Figure 85.3). Plagiocephaly may also result from malpositioning in utero or after birth, a condition referred to as nonsynostotic, deformational, or positional plagiocephaly. The skull has been likened to a parallelogram in appearance in cases that also include involvement of the facial structures. Torticollis, which often is attributed to injury to the sternocleidomastoid muscle at birth (see Chapter 119) and abnormal positioning after birth, contributes to plagiocephaly. Plagiocephaly-torticollis sequence occurs in 1 in 300 live births. Malar and contralateral occipital flattening related to preferential positioning by infants are characteristically seen in affected infants. Some affected babies also have hip dislocation or positional talipes (ie, clubfoot) from in utero constraint (see Chapter 113).

Since 1994 with the advent of the Back to Sleep campaign (currently called the Safe to Sleep campaign), the prevalence of positional plagiocephaly has increased significantly, with estimates of between 25% and 45% of infants affected. Most cases are mild and correct over time. Positional plagiocephaly may encompass positional occipital plagiocephaly (ie, unilateral flattening of parieto-occipital region, compensatory anterior shift of the ipsilateral ear, bulging of the ipsilateral forehead) and positional brachycephaly (ie, symmetric flattening of the occiput, foreshortening of the anterior dimension of the skull, compensatory biparietal widening) or any combination of these 2 deformities. An important strategy to help minimize the development of positional plagiocephaly is to recommend “tummy time,” placing an infant in a prone position while awake (eg, with each diaper change) to help develop the muscles of the neck.

Differential Diagnosis

Typically, the differential diagnosis of clefts of the lip and palate presents few problems. Submucosal clefts may be more difficult to diagnose, however. The child with such a cleft may present with recurrent otitis media, hypernasal speech, or nasal regurgitation of liquids. Physical examination may reveal a bifid uvula and occasionally a notch at the junction of the hard and soft palates.

Determining whether any physical finding represents an isolated anomaly or is part of a genetic syndrome may be challenging. Any associated anomalies (eg, syndactyly, atrial septal defect) suggest the possibility of a genetic problem (Boxes 85.2 and 85.3).

Microtia does not present a diagnostic dilemma. The anomaly usually appears sporadically as an isolated condition, although, like a cleft, it may be part of some other syndrome. Microtia is associated with midfacial hypoplasia and antimongoloid slant to the eyes in Treacher Collins syndrome. Microtia may also occur in oculoauriculovertebral dysplasia (ie, Goldenhar syndrome), which is characterized by several associated findings, including hemifacial microsomia (ie, 1 side of the face smaller than the other), epi-bulbar dermoids, hemivertebrae, microphthalmos, and renal and cardiac anomalies.

Figure 85.2. Changes in the shape of the skull when sutures fuse prematurely. Growth occurs parallel to the fused suture.

Craniosynostosis may also be an isolated finding or associated with a condition such as Apert syndrome, in which clefts of the palate are also seen (Box 85.4). A careful neurodevelopmental assessment helps determine whether microcephaly is related to an underlying neurodevelopmental disorder. Plagiocephaly may present a diagnostic dilemma: Is the condition related to unilateral craniosynostosis, torticollis, or supine sleeping? A careful assessment of the neck for masses or mobility helps determine the role of the neck musculature in cranial flattening and defines the management approach (eg, neck exercises).

Evaluation

Care must be taken to assess the child and determine if the anomaly is an isolated finding or a component of a syndrome. This information is important in terms of patient care and genetic counseling for the parent(s) on the likelihood of having future offspring with similar anomalies.

History

A medical, family, and psychosocial history should be obtained (Box 85.5). Whether the condition appeared at birth or some time later is particularly significant in lesions affecting the skull, such as craniosynostosis. Maternal use of certain medications, such as diazepam, phenytoin, and isotretinoin (eg, Accutane, Claravis), and alcohol is associated with an increased incidence of clefts of the lip and palate. Maternal smoking also increases the risk of clefting, especially in a genetically vulnerable population. Maternal smoking and high altitude are associated with an increased occurrence of craniosynostosis.

Physical Examination

Height, weight, and head circumference should be measured and plotted at each visit. Head circumference is especially important in the child with craniosynostosis or facial asymmetry. The skull should be palpated to detect perisutural ridging. Inner canthal distance may reveal hypotelorism, a finding that occurs in trigonocephaly. The child’s face should be assessed when neutral and when crying or smiling to evaluate the status of the depressor anguli oris muscle. The neck should be palpated for masses and neck range of motion assessed. The growth of the child with craniofacial anomaly must be carefully monitored. Problems with adequate weight gain are frequently experienced by newborns and infants with clefts.

Figure 85.3. Top row, Classic appearance of an infant with facial asymmetry secondary to plagiocephaly. Bottom row, Classic appearance of infants with craniosynostosis.

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